We will explore the metabolic processes of high temperature strains of E. histolytica (potential pathogens) and the low temperature strains in monobacterial and axenic culture seeking underlying differences which may shed light on the reasons for pathogenicity exhibited by parasitic amebae. The glycolytic pathway from glucose or glycogen to end products will be fully defined. The three usual enzymes of this pathway, pyruvate-phosphate dikinase, P-enolpyruvate carboxytransphosphorylase, and the NADP-dependent alcohol dehydrogenase, will be studied with regard to distribution, properties, and the possibility of blocking amebal metabolism by drugs aimed specifically at these enzymes which are so different from those possessed by the human host. Enzyme catalyzed cross-over points between carbohydrate and amino acid metabolism will be studied by means of isotopic label. Anaplerotic sequences in amebal metabolism will be studied and in particular attempts will be made to understand the function of succinate dehydrogenase, the enzyme cleaving 6-phosphogluconate to triose phosphate and pyruvate, and the means of hydrogen production. Recent developments in large lot cultivation of monobacterial and axenic amebae set the stage for the in-depth study of amebal metabolism. BIBLIOGRAPHIC REFERENCES: Acetate Kinase (Pyrophosphate). A fourth pyrophosphate-dependent kinase from Entamoeba histolytica. R.E. Reeves and J.D. Guthrie. Biochem. biophys. Res. Comm. (1975)66, 1389-1395. 6-Phosphofrictokinase (Pyrophosphate). Properties of the enzyme from Entamoeba histolytica and its reaction mechanism. R.E. Reeves, R. Serrano, and D.J. South (1976). J. Biol. Chem. 251, 2958-2962.